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Biodegradable Synthetic Polymers for Tissue

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Biodegradable Synthetic Polymers for Tissue PEuropean A Gunatillake Cells &and R MaterialsAdhikari Vol. 5. 2003 (pages 1-16) DOI: 10.22203/eCM.v005a01 Polymers for tissue ISSN engineering 1473-2262 BIODEGRADABLE SYNTHETIC POLYMERS FOR TISSUE ENGINEERING Pathiraja A.Gunatillake and Raju Adhikari CSIRO Molecular Science, Bag 10, Clayton South MDC, Vic 3169, Australia Abstract Introduction This paper reviews biodegradable synthetic polymers fo- Biodegradable synthetic polymers offer a number of ad- cusing on their potential in tissue engineering applica- vantages over other materials for developing scaffolds in tions. The major classes of polymers are briefly discussed tissue engineering. The key advantages include the abil- with regard to synthesis, properties and biodegradability, ity to tailor mechanical properties and degradation ki- and known degradation modes and products are indicated netics to suit various applications. Synthetic polymers based on studies reported in the literature. A vast major- are also attractive because they can be fabricated into ity of biodegradable polymers studied belongs to the poly- various shapes with desired pore morphologic features ester family, which includes polyglycolides and conducive to tissue in-growth. Furthermore, polymers can polylactides. Some disadvantages of these polymers in tis- be designed with chemical functional groups that can sue engineering applications are their poor induce tissue in-growth. biocompatibility, release of acidic degradation products, Biodegradable synthetic polymers such as poor processability and loss of mechanical properties very poly(glycolic acid), poly(lactic acid) and their copoly- early during degradation. Other degradable polymers such mers, poly(p-dioxanone), and copolymers of trimethyl- as polyorthoesters, polyanhydrides, polyphosphazenes, and ene carbonate and glycolide have been used in a number polyurethanes are also discussed and their advantages and of clinical applications (Shalaby, 1988; Holland and disadvantages summarised. With advancements in tissue Tighe, 1992; Hayashi , 1994; Kohn and Langer, 1997; engineering it has become necessary to develop polymers Ashammakhi and Rokkanen, 1997). The major applica- that meet more demanding requirements. Recent work has tions include resorbable sutures, drug delivery systems focused on developing injectable polymer compositions and orthopaedic fixation devices such as pins, rods and based on poly (propylene fumarate) and poly (anhydrides) screws (Behravesh et al., 1999; Middleton and Tipton, to meet these requirements in orthopaedic tissue engineer- 2000). Among the families of synthetic polymers, the ing. Polyurethanes have received recent attention for de- polyesters have been attractive for these applications be- velopment of degradable polymers because of their great cause of their ease of degradation by hydrolysis of ester potential in tailoring polymer structure to achieve me- linkage, degradation products being resorbed through the chanical properties and biodegradability to suit a variety metabolic pathways in some cases and the potential to of applications. tailor the structure to alter degradation rates. Polyesters have also been considered for development of tissue en- Key Words: Biodegradable polymers, tissue engineering, gineering applications (Hubbell, 1995; Thomson et al degradation, injectable polymers 1995a, Yazemski et al. 1996; Wong and Mooney, 1997), particularly for bone tissue engineering (Kohn and Langer, 1997; Burg et al., 2000). Attempts to find tissue-engineered solutions to cure orthopaedic injuries/diseases have made necessary the development of new polymers that meet a number of de- manding requirements. These requirements range from the ability of scaffold to provide mechanical support dur- ing tissue growth and gradually degrade to biocompatible products to more demanding requirements such as the ability to incorporate cells, growth factors etc and pro- vide osteoconductive and osteoinductive environments. Furthermore, the development of in-situ polymerizable Address for correspondence: compositions that can function as cell delivery systems Pathiraja A. Gunatillake in the form of an injectable liquid/paste are becoming CSIRO Molecular Science, Bag 10, increasingly attractive in tissue engineering applications. Clayton South MDC, Many of the currently available degradable polymers do Vic 3169, not fulfil all of these requirements and significant chemi- Australia cal changes to their structure may be required if they are Telephone number: 61 3 9545 2501 to be formulated for such applications. E-mail: [email protected] Scaffolds made from synthetic and natural polymers, 1 P A Gunatillake & R Adhikari Polymers for tissue engineering and ceramics have been investigated extensively for or- Major classes of degradable polymers thopaedic repair. This approach has advantages such as the ability to generate desired pore structures, matching Polyesters size, shape and mechanical properties to suit a variety of A vast majority of biodegradable polymers studied be- applications. However, shaping these scaffolds to fit cavi- long to the polyester family. Table 1 lists the key poly- ties/defects with complicated geometries, bonding to the mers in this family. Among these poly(α-hydroxy acids) bone tissues, and incorporating cells and growth factors, such as poly(glycolic acid) (PGA), poly(lactic acid) (PLA), and requirement of open surgery are a few major disad- and a range of their copolymers have historically com- vantages of this approach. prised the bulk of published material on biodegradable A material that can be used as a scaffold in tissue polyesters and have a long history of use as synthetic bio- engineering must satisfy a number of requirements. These degradable materials (Shalaby, 1988; Holland and Tighe, include biocompatibility, biodegradation to non toxic 1992; Hayashi , 1994: Kohn and Langer, 1997; products within the time frame required for the applica- Ashammakhi and Rokkanen, 1997) in a number of clini- tion, processability to complicated shapes with appropri- cal applications. These polymers have been used as su- ate porosity, ability to support cell growth and prolifera- tures (Cutright et al., 1971) plates and fixtures for frac- tion, and appropriate mechanical properties, as well as ture fixation devices (Mayer and Hollinger, 1995) and maintaining mechanical strength during most part of the scaffolds for cell transplantation (Thomson et al. 1995b). tissue regeneration process. Development of a degrada- ble polymer composition that can be injected Poly(glycolic acid), poly(lactic acid) and their arthroscopically has number of advantages in tissue en- copolymers gineering as against prefabricated scaffolds. A major ad- Poly(glycolic acid) (PGA) is a rigid thermoplastic mate- vantage would be the possibility of administering the gel rial with high crystallinity. (46-50%). The glass transi- arthroscopically avoiding surgery in many cases. It also tion and melting temperatures of PGA are 36 and 225ºC, has the advantage of filling cavities with complex respectively. Because of high crystallinity, PGA is not geometries, and to provide good bonding to tissue. Cells, soluble in most organic solvents; the exceptions are highly growth factors and other components to support cell fluorinated organic solvents such as hexafluoro isopro- growth could also be incorporated with the gel. Such poly- panol. mer systems also have the potential to be formulated to Although common processing techniques such as ex- generate porous structure upon curing to facilitate nutri- trusion, injection and compression moulding can be used ent flow to cells during growth and proliferation. Fur- to fabricate PGA into various forms, its high sensitivity ther, such polymers may be useful in pre-fabricating scaf- to hydrolytic degradation requires careful control of folds with complex shapes with appropriate pore struc- processing conditions (Mikos and Temenoff, 2000, Jen tures with biological components incorporated. However, et al. 1999). Porous scaffolds and foams can also be fab- in addition to the main requirements mentioned above, ricated from PGA, but the properties and degradation an injectable polymer composition must meet the follow- characteristics are affected by the type of processing tech- ing requirements to be useful in tissue engineering appli- nique. Solvent casting, particular leaching method and cations. Ideally the prepolymer should be in liquid/paste compression moulding are also used to fabricate PGA from, sterilizable without causing any chemical change, based implants. and have the capacity to incorporate biological matrix The preferred method for preparing high molecular components. Upon injection the prepolymer mixture weight PGA is ring-opening polymerization of glycolide should bond to biological surface and cures to a solid and (Figure 1), the cyclic dimer of glycolic acid (Hollinger et porous structure with appropriate mechanical properties al. 1997, Sawhney and Drumheller, 1998), and both so- to suit the application. The curing should be with mini- lution and melt polymerization methods can be used. The mal heat generation and the chemical reactions involved common catalysts used include organo tin, antimony, or in curing should not damage the cells or adjacent tissues. zinc. If stannous octoate is used, temperature of approxi- The cured polymer while facilitating cell in-growth, pro- mately 175ºC is required for a period of 2 to 6 hours for liferation and migration, should ideally be degraded
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